United States Value Set for the Functional Assessment of Cancer Therapy-General Eight Dimensions (FACT-8D), a Cancer-Specific Preference-Based Quality of Life Instrument.

OBJECTIVES: To develop a value set reflecting the United States (US) general population's preferences for health states described by the Functional Assessment of Cancer Therapy (FACT) eight-dimensions preference-based multi-attribute utility instrument (FACT-8D), derived from the FACT-General cancer-specific health-related quality-of-life (HRQL) questionnaire. METHODS: A US online panel was quota-sampled to achieve a general population sample representative by sex, age (≥ 18 years), race and ethnicity. A discrete choice experiment (DCE) was used to value health states. The valuation task involved choosing between pairs of health states (choice-sets) described by varying levels of the FACT-8D HRQL dimensions and survival (life-years). The DCE included 100 choice-sets; each respondent was randomly allocated 16 choice-sets. Data were analysed using conditional logit regression parameterized to fit the quality-adjusted life-year framework, weighted for sociodemographic variables that were non-representative of the US general population. Preference weights were calculated as the ratio of HRQL-level coefficients to the survival coefficient. RESULTS: 2562 panel members opted in, 2462 (96%) completed at least one choice-set and 2357 (92%) completed 16 choice-sets. Pain and nausea were associated with the largest utility weights, work and sleep had more moderate utility weights, and sadness, worry and support had the smallest utility weights. Within dimensions, more severe HRQL levels were generally associated with larger weights. A preference-weighting algorithm to estimate US utilities from responses to the FACT-General questionnaire was generated. The worst health state's value was -0.33. CONCLUSIONS: This value set provides US population utilities for health states defined by the FACT-8D for use in evaluating oncology treatments.

Real-world systemic therapy treatment patterns for squamous cell carcinoma of the head and neck in Canada.

Background: In the present study, we examined real-world treatment patterns for squamous cell carcinoma of the head and neck (scchn) in Canada, which are largely unknown. Methods: Oncologists across Canada provided data for disease history, characteristics, and treatment patterns during May-July 2016 for 6-8 consecutive patients receiving first-line or second-line drug treatment for scchn (including locally advanced and recurrent or metastatic disease). Results: Information from 16 physicians for 109 patients receiving drug treatment for scchn was provided; 1 patient was excluded from the treatment-pattern analysis. Median age in the cohort was 63 years [interquartile range (iqr): 57-68 years], and 24% were current smokers, with a mean exposure of 26.2 ± 12.7 pack-years. The most common tumour site was the oropharynx (48%). Most patients (84%) received platinum-based regimens as first-line treatment (44% received cisplatin monotherapy). Use of cetuximab-based regimens as first-line treatment was limited (17%). Of 53 patients receiving second-line treatment, 87% received a first-line platinum-based regimen. Median time between first-line treatment with a platinum-based regimen and initiation of second-line treatment was 55 days (iqr: 20-146 days). The most common second-line regimen was cetuximab monotherapy (43%); platinum-based regimens were markedly infrequent (13%). Conclusions: Our analysis provides real-world insight into scchn clinical practice patterns in Canada, which could inform reimbursement decision-making. High use of platinum-based regimens in first-line drug treatment was generally reflective of treatment guidelines; cetuximab use in the second-line was higher than anticipated. Additional real-world studies are needed to understand the effect of novel therapies such as immuno-oncology agents on clinical practice and outcomes, particularly for recurrent or metastatic scchn.

Greater occipital nerve block using local anaesthetics alone or with triamcinolone for transformed migraine: a randomised comparative study.

OBJECTIVE: To determine whether adding triamcinolone to local anaesthetics increased the efficacy of greater occipital nerve block (GONB) and trigger-point injections (TPIs) for transformed migraine (TM). METHODS: Patients with TM were randomised to receive GONB and TPIs using lidocaine 2% and bupivacaine 0.5% + either saline or triamcinolone 40 mg. We assessed the severity of headache and associated symptoms before and 20 minutes after injection. Patients documented headache and severity of associated symptoms for 4 weeks after injections. Changes in symptom severity were compared between the two groups. RESULTS: Thirty-seven patients were included. Twenty minutes after injection, mean headache severity decreased by 3.2 points in group A (p<0.01) and by 3.1 points in group B (p<0.01). Mean neck pain severity decreased by 1.5 points in group A (p<0.01) and by 1.7 points in group B (p<0.01). Mean duration of being headache-free was 2.7+/-3.8 days in group A and 1.0+/-1.1 days in group B (p = 0.67). None of the outcome measures differed significantly between the two groups. Both treatments were well tolerated. CONCLUSIONS: Adding triamcinolone to local anaesthetics when performing GONB and TPIs was not associated with improved outcome in this sample of patients with TM.

Identifying cutaneous allodynia in chronic migraine using a practical clinical method.

Cutaneous allodynia is common in migraine. In the majority of previous studies on allodynia in migraine, only patients with episodic migraine (EM) were included. Little is known on patterns of allodynia in chronic migraine (CM). Since the presence of allodynia is associated with a poor response to triptans, a clinically practical method to test migraine patients for allodynia would be useful to the clinician. The aim of this study was to assess the prevalence of dynamic mechanical (brush) allodynia (BA) in CM, using a clinically practical method. Eighty-nine CM patients were prospectively recruited. Patients were given a structured questionnaire regarding demographic data and migraine characteristics. Allodynia was tested using a 10 x 10-cm gauze pad to brush various areas of the skin lightly. The prevalence of BA in the entire study population and in different patient subgroups was calculated. BA was present in 42.7% (38/89) of the patients. The presence of allodynia was unrelated to age, disease duration or to the occurrence of an acute headache exacerbation at the time of testing. Allodynia was positively associated with a history of migraine aura. BA was most common in the cephalic area, but was also seen in cervical dermatomes. BA is common in CM and, unlike in EM, is not significantly affected by the occurrence of an acute headache exacerbation. This suggests that central trigeminovascular neurons are chronically sensitized in patients experiencing migraine headache >15 days per month. The testing of BA in the clinical setting is possible using a simple and brief approach. It allows the clinician to determine whether the patient is sensitized, a diagnosis that affects treatment decisions.

Responsiveness of the Smoking Cessation Quality of Life (SCQoL) questionnaire.

BACKGROUND: The Smoking Cessation Quality of Life (SCQoL) questionnaire was developed to quantify changes in self-reported functioning and well-being associated with the smoking cessation process and to facilitate comparisons among smokers, former smokers, and nonsmokers. The SCQoL includes 5 cessation-targeted scales and the 8 multi-item scales of the Medical Outcomes Study 36-Item Short-Form Health Survey. OBJECTIVE: This study was conducted to assess the responsiveness of the SCQoL by analyzing associations between SCQoL scale scores and duration of smoking abstinence. METHODS: The SCQoL was administered at a screening visit and 2 to 6 weeks after screening as part of a longitudinal study. Study participants included smokers who intended to quit smoking. Subjects were required to purchase nicotine inhalers and were prompted to quit smoking before follow-up. Based on self-reported duration of abstinence at follow-up, subjects were categorized as recidivists (0 days smoke free), short-term abstainers (1-7 days smoke free), or longer-term abstainers (>7 days smoke free). Kruskal-Wallis tests were used to compare changes in scale scores from screening to follow-up among the 3 groups. RESULTS: The internal consistency reliability of the 13 SCQoL scales ranged from 0.67 to 0.92. Subjects who maintained abstinence for longer periods experienced smaller declines in health-related quality of life between the screening and follow-up assessments. Differences among the 3 groups were driven primarily by differences between recidivists and longer-term abstainers. CONCLUSIONS: The results are consistent with research indicating that recidivists report a greater number of (and more severe) cessation-related symptoms than abstainers. The findings of this investigation provide evidence for the responsiveness of the SCQoL.

Health care utilization by migraine patients: a 1998 Medicaid population study.

BACKGROUND: In the last decade, a number of studies have documented the economic impact of migraine headaches on society. Although previous research has shown that patients with migraine headache consume a greater amount of health care resources than those without migraine, the economic impact of this condition on a Medicaid population has not been assessed. OBJECTIVE: The purpose of this study was to compare the health care resource utilization of-patients with and without migraine headache in the Idaho Medicaid population. METHODS: Idaho Medicaid claims from 1998 were reviewed to identify cases and controls. Four controls, matched for age, sex, race, and residence, were obtained for each case. Physician services, hospital services, emergency room services, and prescription use were compared between the 2 groups. Multivariate analyses were performed to determine differences between the 2 groups after controlling for potential confounders. RESULTS: Eighty percent of the cases were female, and 94% of the patients were white. Patients with migraine headache had statistically significantly higher health care resource consumption than matched controls (P < 0.05). Total log costs for prescription use, physician services, and hospital services were significantly higher (P < 0.001) in the migraine group even after controlling for migraine-associated comorbid conditions and demographic variables. CONCLUSIONS: Total health care costs for migraine patients were 1.6 times higher than for matched controls. The results of this study suggest that migraine is a significant economic burden to the Medicaid program.

Fatal airway compromise due to retropharyngeal hematoma after airbag deployment.

In trauma patients it is possible for a hematoma to form in the potential space between the pharynx and cervical spine (the retropharyngeal space). Fewer than 30 cases of actual airway obstruction secondary to retropharyngeal hematomas have been reported. We present an unusual case of an elderly woman who was involved in a minor motor vehicle collision which deployed her airbag. She died as a result of anoxic injury to the brain. Autopsy results demonstrated transverse fractures through the bodies of C5 and C7 with associated significant retropharyngeal and mediastinal hematoma. Airbags have been shown to significantly decrease the mortality rate in frontal collisions; however, the potential for hyperextension injuries from airbag deployment exists, especially if the occupant is unrestrained, small, or sitting too close to the airbag. When this woman's airbag deployed, it most likely caused her vertebral fractures, hematoma, subsequent airway compromise, and anoxic brain injury. Whatever the mechanism of trauma, one must be cognizant of the potential risk for retropharyngeal hematoma and airway compromise when a patient presents with injury to the cervical spine.

Aortic bifurcation reconstruction: use of the Memotherm self-expanding nitinol stent for stenoses and occlusions.

PURPOSE: To assess the technical success, initial clinical outcome, and intermediate follow-up of the Memotherm nitinol self-expanding stent in aortic bifurcation reconstruction. METHODS: Thirty-three patients (13 male, 20 female), mean age 64 years, were treated, who had symptoms classified by the Surgical Vascular Society/International Society of Cardiovascular Surgery (SVS/ICVS) classification as grade 2 in 11 (33%), grade 3 in 19 (58%) and grade 4 in 3 (9%) patients. Lesions were classified according to severity and type. Indications for placement of a Memotherm nitinol self-expanding stent were failed angioplasty in 14 (42%), chronic occlusions in 12 (37%), and complex stenoses in seven (21%) patients. RESULTS: Sixty-seven stents were technically successfully placed in 66 aorto-iliac segments in 33 patients, with one major complication. Initial clinical outcome was improvement in 25 (81%), no change in four (13%), and a worsening in two (6%) patients by Rutherford criteria. Mean early ankle/brachial pressure index (ABI) gain was 0. 27 for occlusions and 0.05 for stenoses. Clinical follow-up was obtained in all patients, with retrospective angiographic follow-up in 28 (85%) at a mean of 16 months (range 12-26 months). The decrease in ABI and the decrease in angiographic luminal diameter at follow-up was determined as the "late loss." The mean ABI late losses were -0.06, 0.00, and 0.09, and the mean angiographic late losses were 6.7%, 10% and 14% for occlusions, stenoses, and normal segments respectively. Primary clinical patency was 96%, primary angiographic patency was 89%, and secondary angiographic patency was 93%. CONCLUSION: The high technical success of stent placement, the low complication rates for aortic bifurcation reconstruction using the Memotherm self-expanding stent, and high clinical and angiographic patency maintained at intermediate follow-up support their use in aortic bifurcation reconstruction.

Development of the Smoking Cessation Quality of Life questionnaire.

This paper describes the development of the Smoking Cessation Quality of Life (SCQoL) questionnaire, a self-reported measure designed to quantify the impact of smoking cessation on perceived functioning and well-being in adults. In addition to incorporating the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) as a generic core, the SCQoL contains 5 multi-item cessation-targeted scales: social interactions, self-control, sleep, cognitive functioning, and anxiety. The draft SCQoL was developed through a series of focus groups and was pilot-tested in a sample of 101 adults. Respondents were predominantly male (59.2%), with a mean (SD) age of (48.6) (12.7) years and a mean (SD) smoking history of 29.3 (14.7) years. Of the respondents, 76.5% identified themselves as current smokers and 23.5% indicated that they were former smokers. The majority of former smokers (82.6%) reported being abstinent for > or =2 weeks. Multivariate analysis of variance was used to compare scale scores between smokers and former smokers who had been abstinent for > or =2 weeks. Former smokers reported significantly higher scores than did current smokers on 3 of 8 SF-36 scales and 3 of 5 cessation-targeted scales (P < 0.05). In no case did current smokers report significantly higher scale scores than did former smokers. The internal-consistency reliability of the SCQoL scales ranged from 0.68 to 0.96, exceeding 0.70 on 12 of 13 scales. These findings provide preliminary evidence for the reliability and construct validity of the SCQoL.

CT brain scans after acute stroke: how far are we from meeting the Scottish intercollegiate guidelines network (SIGN) recommendations? Results from the year prior to guideline publication.

OBJECTIVE: To determine what proportion of patients admitted to Ninewells Hospital & Medical School in 1996 with acute stroke underwent CT brain scans and in what time frame. To decide if the targets set by the SIGN guidelines can be met, and if not, the reasons for this. DESIGN: Data from the Dundee Ninewells Stroke Register and the Computerised Radiology Information System were used to determine the timing of CT scanning in relation to stroke and admission. Notes were also reviewed to determine why CT scans had not been done in some patients. SETTING: Departments of Medicine and Radiology, Ninewells Hospital & Medical School Dundee. SUBJECTS: All patients admitted with acute stroke in the calendar year 1996. RESULTS: Two hundred and eighty six patients presented with acute stroke in 1996. Of these patients, 250 patients (87%) had a CT brain scan. Eighty three (29%) underwent CT brain scanning within 48 hours of the acute event. A total of 163 (57%) were scanned within a week. Two hundred and thirty three (81%) were scanned within three weeks. Thirty six patients were not scanned after their acute event and the reasons recorded are reviewed. CONCLUSIONS: Less than two-thirds of patients were scanned within the time interval of seven days recommended in the SIGN Guidelines for stroke management. Implementation of the current SIGN Guidelines will therefore, require reorganisation of the service to ensure that all patients receive scans within seven and preferably within two days and may have resource implication.

Management of iliac occlusions with a new self-expanding endovascular stent.

OBJECTIVES: To determine the patency and acceptability of the Memotherm endovascular stent in the treatment of iliac arterial occlusions. MATERIALS AND METHODS: Twenty-two patients (12 males and 10 females) underwent stenting of iliac occlusions of the aortoiliac bifurcation, the common iliac artery and the external iliac artery. All patients were reassessed at 3, 6 and 12 month intervals and then yearly to evaluate their symptoms and Doppler pressure measurements. Comparison was made with results from other studies treating iliac occlusions by angioplasty alone or combined with stenting. RESULTS: Out of 22 patients, 21 had an immediate and sustained improvement over the whole of the follow-up period. The Ankle-brachial Index (ABI) increased from a mean value of 0.49 to 0.81 3-months postprocedure and improved to 0.85 at 12 months (paired t-test p < 0.001). At 6 and 12 months the stent patency remained at 95.5%, which compares favourably with other studies. There were four minor and one major complication associated with the stenting procedure. CONCLUSIONS: The Memothern self-expanding stent is a useful, safe and effective device suitable for the majority of iliac occlusions. Further long-term evaluation is warranted to confirm its advantages over open surgery.

The white blood cell adhesion molecule E-selectin predicts restenosis in patients with intermittent claudication undergoing percutaneous transluminal angioplasty.

BACKGROUND: Experimental studies have shown that endothelial dysfunction is an early event preceding restenosis. Monocytes and neutrophils have been shown to bind to damaged endothelium via the cell adhesion molecules (CAMs). The selectins are involved in capturing the leukocytes and tethering them to the endothelium. E-selectin is a CAM that is only expressed on activated endothelial cells. Its ligands are expressed on monocytes and neutrophils and it has been found to exist in a soluble form. This soluble form may represent a marker for endothelial damage and may be a precursor of smooth muscle proliferation. METHODS AND RESULTS: Fifty-four patients who were undergoing peripheral arterial balloon angioplasty had blood sampled before angioplasty. E-selectin was measured in plasma with the use of an ELISA. At follow-up angiogram, 30% (n=14) of the patients had restenosed at 1 year. There was a significant difference in baseline E-selectin levels in patients who restenosed compared with those who did not (65.3 ng/mL [58.25 to 78.05] versus 52.3 [34.2 to 62.1], Mann-Whitney U, P<.007). Endothelial activation with subsequent adherence of white blood cells is an important step in restenosis. CONCLUSIONS: We have shown an increased level of shed E-selectin in patients destined for restenosis and suggest that this work further supports a role for white blood cell/endothelial interaction in restenosis after angioplasty.

Loss of expression of transforming growth factor beta type I and type II receptors correlates with tumor grade in human prostate cancer tissues.

Transforming growth factor beta1 (TGF-beta1) is a potential regulator of prostate cancer cell growth that signals through a heteromeric complex composed of type I and type II receptors. In the present study, an attempt was made to establish a correlation between expression of TGF-beta receptors and tumor grade in archival human prostate cancer tissues. To this end, immunohistochemical studies for TGF-beta receptors were carried out on 32 cases of human prostate cancer and 8 samples of benign human prostate. In both benign and malignant human prostate tissues, immunoreactivity for both type I and type II receptors was detected predominantly in epithelial cells. In addition, there was an inverse correlation between the loss of expression of TGF-beta1 type I and type II receptors and the tumor grade. Of the 32 prostate cancer cases screened, staining was completely absent in four samples for type II receptor (P < 0.05) and eight samples for type I receptor (P < 0.025). In contrast, all eight samples of benign prostate tissues investigated in this study showed strong staining for both type I and type II receptors. These results, taken together, indicate that human prostate cancer cells frequently have loss of expression of TGF-beta type I and/or type II receptors. Furthermore, these observations provide a potential mechanism for prostate cancer cells to escape the growth-inhibitory effect of TGF-beta.

Genetic change in transforming growth factor beta (TGF-beta) receptor type I gene correlates with insensitivity to TGF-beta 1 in human prostate cancer cells.

Transforming growth factor beta 1 (TGF-beta 1), a potential regulator of growth of prostate cancer cells, exerts its effects through interaction with membrane receptors. In the present study, an attempt was made to establish a correlation between TGF-beta 1 sensitivity and TGF-beta receptor expression in three prostate cancer cell lines (PC3, DU145, and LNCaP). In a dose-dependent manner, TGF-beta 1 inhibited the proliferation of PC3 and DU145 cells but not LNCaP cells. Since TGF-beta signals through a heteromeric complex composed of TGF-beta receptors type II and type I, the expression of these receptors was investigated by Western blot analysis and reverse transcriptase-PCR. These studies demonstrated that all three prostate cancer cell lines express type II receptor. In contrast, type I receptor was detected only in the TGF-beta 1-sensitive PC3 and DU145 cells but not in the TGF-beta 1-insensitive LNCaP cells. To investigate the possibility that the undetectable expression of type I receptor in LNCaP cells is due to a change in the respective gene, Southern blot analysis was performed. The result demonstrated that there was a genetic change in type I receptor gene in these cells. Subsequently, when LNCaP cells were transiently transfected with T beta R-I cDNA, sensitivity to TGF-beta 1 was restored. These observations indicate that LNCaP cells contain a defective T beta R-I gene which rendered these cells insensitive to the action of TGF-beta 1.

The use of the Wallstent in aorto-iliac vascular disease.

Forty-three patients had self-expanding endovascular Wallstents inserted for aorto-iliac arterial disease. A total of 59 Wallstents were inserted into 50 iliac arteries. There were 27 males and 16 females with a mean age of 62.51 years. Included in the series were 19 iliac occlusions, 21 severe atheromatous disease of the aortoiliac segment, two severe dissections following conventional angioplasty and one re-stenosis of a previously dilated iliac segment. All of the stents were successfully deployed but there were five significant complications. One case of distal embolism was treated by surgical embolectomy but the other four were treated by an additional percutaneous technique. At follow-up after 6 months all patients remain symptomatically improved. Aorto-iliac stenting is a cost-effective treatment in selected cases of severe aorto-iliac disease.

Increased activity of oxygen free radicals during reperfusion in patients with peripheral arterial disease undergoing percutaneous peripheral artery balloon angioplasty.

Modern balloon angioplasty plays an important role in the treatment of localized arterial lesions in patients with peripheral vascular disease (PVD). However, the process of angioplasty produces a situation of acute ischaemia followed by reperfusion and animal studies have shown such situation to be associated with an increase in free radical (FR) generation. FRs cause tissue damage and may be prothrombotic and may therefore contribute to the occurrence of restenosis. Release of FRs during reperfusion has not been fully investigated in humans. We studied the FR activity in 44 patients with PVD in the superficial or popliteal arteries receiving angioplasty treatment. Thirty patients had stenotic lesions and 14 had totally occlusive disease. Baseline blood samples were taken from the arterial catheter for the assay of malondialdehyde (MDA) (spectrophotometric thiobarbituric acid assay) immediately before and after balloon inflation. MDA is a measure of lipid peroxidation which is an indicator of FR activity. MDA levels during reperfusion were significantly higher than those immediately prior to balloon inflation [8.4 (0.29) vs 8.1 (0.24) mumol/l, respectively; mean increase--0.34 (0.13) mumol/l; [mean (sem)] p less than 0.01 (paired Wilcoxon rank test)] in the stenotic lesions. Such changes were not observed in the totally occlusive lesions [7.26 (0.39) vs 7.26 (0.48) mumol/l, respectively; p = 0.75]. Our study has shown increased FR release following angioplasty in patients with stenotic, but not occlusive, peripheral vascular lesions. Angioplasty of the stenotic lesions creates++ a situation of acute ischaemia and reperfusion whereas that of the occlusive lesions leads to the reperfusion of a chronically ischaemic area.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical and radiological features of osteogenesis imperfecta type IVA.

This paper reports a survey of 78 patients with osteogenesis imperfecta (OI) type IVA, the variant that causes the greatest difficulties in differential diagnosis. A subgroup of children aged between five and eleven were compared with a control group from local schools. Among the OI children there were, apart from the high number of fractures, also significantly increased incidences of bruising, nosebleeds, excessive sweating and hypermobility of joints. Although none of the children with OI type IV had the dark blue or grey sclerae of the type I disease, an appreciable number had pale blue sclerae in early childhood. Radiologically normal bone texture was seen at the time of the first fracture in 10 out of 17 patients. Hypertrophic callus was seen in five patients and metaphyseal fractures in four. We hope that the information on this large group of patients will assist in the prevention of diagnostic difficulties.

Subcutaneous calcium heparin versus intravenous sodium heparin in treatment of established acute deep vein thrombosis of the legs: a multicentre prospective randomised trial.

One hundred patients with phlebographically proved acute deep vein thrombosis of the legs were prospectively randomised into two treatment groups to compare the safety and efficacy of subcutaneous calcium heparin versus intravenous sodium heparin administered by constant infusion pump. The dose of heparin was determined by daily measurement of the kaolin cephalin clotting time. Treatment was maintained for up to 14 days, after which phlebography was repeated. Of 49 patients who received subcutaneous calcium heparin, two showed an increase in thrombus size, while eight showed complete lysis. In the 47 patients who received intravenous sodium heparin thrombus increased in size in 13 while only one showed evidence of complete lysis. These differences were significant. There were no significant differences between the two groups in the incidence of serious complications, although almost half of those receiving intravenous heparin had some minor problem with the constant infusion pump and just over half of those receiving subcutaneous heparin had some bruising at the injection site. This study showed that subcutaneous calcium heparin was more effective in helping lyse existing thrombus and preventing its propagation than intravenous sodium heparin.